The specific aims of this project are to define: 1) the role of circulating vasoactive substances (prostaglandins, other arachidonic acid metabolites, angiotensin II, catecholamines and vasopressin) in the physiological and pharmacological regulation of the perinatal pulmonary circulation, and 2) factors which regulate lung liquid formation and reabsorption in fetal animals prior to birth. An isolated (in-situ), pump perfused, lower left lung preparation in anesthetized, exteriorized fetal goats and sheep will be used to study regulation of blood flow to the lungs. Both acute and chronic studies will be carried out on fetal goats and sheep, respectively, to determine changes in lung fluid formation (using an impermeant tracer technique) and composition. The long term objectives of these studies are to provide a better understanding of the factors which contribute to: 1) regulation of the perinatal pulmonary circulation, and 2) adaptations which must occur in the transition from liquid to air breathing at birth. Knowledge of normal and altered mechanisms of control of the pulmonary circulation and lung liquid formation should be of considerable clinical value in understanding disturbances which may occur in the pulmonary circulation during the perinatal period.